Methane Generation from CO2 with a Molecular Rhenium Catalyst.

The atomic-level tunability of molecular structures is a compelling reason to develop homogeneous catalysts for challenging reactions such as the electrochemical reduction of carbon dioxide to valuable C1-Cn products. Of particular interest is methane, the largest component of natural gas. Herein, we report a series of three isomeric rhenium tricarbonyl complexes coordinated by the asymmetric diimine ligands 2-(isoquinolin-1-yl)-4,5-dihydrooxazole (quin-1-oxa), 2-(quinolin-2-yl)-4,5-dihydrooxazole (quin-2-oxa), and 2-(isoquinolin-3-yl)-4,5-dihydrooxazole (quin-3-oxa) that catalyze the reduction of CO2 to carbon monoxide and methane, albeit the latter with a low efficiency. To our knowledge, these complexes are the first examples of rhenium(I) catalysts capable of converting carbon dioxide into methane. Re(quin-1-oxa)(CO)3Cl (1), Re(quin-2-oxa)(CO)3Cl (2), and Re(quin-3-oxa)(CO)3Cl (3) were characterized and studied using a variety of electrochemical and spectroscopic techniques. In bulk electrolysis experiments, the three complexes reduce CO2 to CO and CH4. When the controlled-potential electrolysis experiments are performed at -2.5 V (vs Fc+/0) and in the presence of the Brønsted acid 2,2,2-trifluoroethanol, methane is produced with turnover numbers that range from 1.3 to 1.8. Isotope labeling experiments using 13CO2 atmosphere produce 13CH4 (m/z = 17) confirming that methane originates from CO2 reduction. Theoretical calculations are performed to investigate the mechanistic aspects of the 8e-/8H+ reduction of CO2 to CH4. A ligand-assisted pathway is proposed to be an efficient pathway in the formation of CH4. Delocalization of the electron density on the (iso)quinoline moiety upon reduction stabilizes the key carbonyl intermediate leading to additional reactivity of this ligand. These results should aid the development of more robust catalytic systems that produce CH4 from CO2.

Synergistic Effects of Imidazolium-Functionalization on fac-Mn(CO)3 Bipyridine Catalyst Platforms for Electrocatalytic Carbon Dioxide Reduction.

The electrocatalytic reduction of carbon dioxide (CO2) could be a powerful tool for generating chemical fuels and feedstock molecules relevant to the chemical industry. One of the major challenges for molecular catalysts remains the necessity of high overpotentials, which can be overcome by identifying novel routes that improve the energetic reaction trajectory of critical intermediates during catalysis. In this combined experimental and computational study, we show that imidazolium functionalization of molecular fac-Mn(CO)3 bipyridine complexes results in CO2 reduction at mild electrochemical potentials in the presence of H2O. Importantly, our studies suggest that imidazolium groups in the secondary coordination sphere promote the formation of a local hydration shell that facilitates the protonation of CO2 reduction intermediates. As such, we propose a synergistic relationship between the functionalized catalyst and H2O, which stands in contrast to other systems in which the presence of H2O frequently has detrimental effects on catalysis.

Elucidating the Solution-Phase Structure and Behavior of 8-Hydroxyquinoline Zinc in DMSO.

The solution-phase structure and electronic relaxation dynamics of zinc bis-8-hydroxyquinoline [Zn(8HQ)2] in dimethyl sulfoxide (DMSO) were examined using a broad array of spectroscopic techniques, complimented by ab initio calculations of molecular structure. The ground-state structure was determined using extended X-ray absorption fine structure (EXAFS) data collected on the Zn K-edge and diffusion ordered spectroscopy (DOSY) NMR. The complex was found to be monomeric and octahedral, with two bidentate 8-hydroxyquinolate ligands and two DMSO molecules coordinated to the zinc through oxygen atoms. Electronic relaxation dynamics were examined with ultrafast transient absorption spectroscopy and complementary density functional calculations. Electronic relaxation was observed to proceed through both singlet and triplet pathways. This solution-phase data provides a deeper physical understanding of the behavior of this molecule, which has a variety of uses such as sensing, OLEDs, and biological applications.

Novel 5-arylthio-5H-chromenopyridines as a new class of anti-fibrotic agents.

Liver fibrosis is a critical wound healing response to chronic liver injury such as hepatitis C virus (HCV) infection. If persistent, liver fibrosis can lead to cirrhosis and hepatocellular carcinoma (HCC). The development of new therapies for preventing liver fibrosis and its progression to cancer associated with HCV infection remains a critical challenge. Identification of novel anti-fibrotic compounds will provide opportunities for innovative therapeutic intervention of HCV-mediated liver fibrosis. We designed and synthesized a focused set of 5-arylthio-5H-chromenopyridines as a new class of anti-fibrotic agents. Liver fibrosis assays demonstrated that the compounds 3a and 3c show inhibitory activity towards human hepatic stellate cells (LX2) activation at 10µM. The HCV NS3 and NS5A proteins in HCV subgenome-expressing cells were also significantly reduced in cells treated with 3a and 3c, suggesting the possible inhibitory role of the compounds in HCV translation/replication activities. We have also examined the reactivity of these compounds with medicinally-relevant metal compounds such as platinum and gold. The reactivity of these complexes with metals and during Mass Spectrometry suggests that CS bond cleavage is relatively facile.

Electrochemical Reduction of CO2 Catalyzed by Re(pyridine-oxazoline)(CO)3Cl Complexes.

A series of rhenium tricarbonyl complexes coordinated by asymmetric diimine ligands containing a pyridine moiety bound to an oxazoline ring were synthesized, structurally and electrochemically characterized, and screened for CO2 reduction ability. The reported complexes are of the type Re(N-N)(CO)3Cl, with N-N = 2-(pyridin-2-yl)-4,5-dihydrooxazole (1), 5-methyl-2-(pyridin-2-yl)-4,5-dihydrooxazole (2), and 5-phenyl-2-(pyridin-2-yl)-4,5-dihydrooxazole (3). The electrocatalytic reduction of CO2 by these complexes was observed in a variety of solvents and proceeds more quickly in acetonitrile than in dimethylformamide (DMF) and dimethyl sulfoxide (DMSO). The analysis of the catalytic cycle for electrochemical CO2 reduction by 1 in acetonitrile using density functional theory (DFT) supports the C-O bond cleavage step being the rate-determining step (RDS) (ΔG⧧ = 27.2 kcal mol-1). The dependency of the turnover frequencies (TOFs) on the donor number (DN) of the solvent also supports that C-O bond cleavage is the rate-determining step. Moreover, the calculations using explicit solvent molecules indicate that the solvent dependence likely arises from a protonation-first mechanism. Unlike other complexes derived from fac-Re(bpy)(CO)3Cl (I; bpy = 2,2'-bipyridine), in which one of the pyridyl moieties in the bpy ligand is replaced by another imine, no catalytic enhancement occurs during the first reduction potential. Remarkably, catalysts 1 and 2 display relative turnover frequencies, (icat/ip)2, up to 7 times larger than that of I.

Electrocatalytic Reduction of CO2 by Group 6 M(CO)6 Species without "Non-Innocent" Ligands.

To understand the electrocatalytic CO2 reduction of metal carbonyl complexes without "non-innocent" ligands, the electrochemical responses of group 6 M(CO)6 (M = Cr, Mo, or W) and group 7 M2(CO)10 (M = Mn or Re) complexes were examined under Ar and CO2 at a glassy carbon electrode. All of the complexes showed changes in their cyclic voltammograms under CO2. The group 6 hexacarbonyl species show a significant increase in current under CO2 during metal-based reduction, corresponding to catalytic reduction of CO2. Bulk electrolysis experiments with Mo(CO)6 showed that CO was the primary product. The group 7 dimers showed very little change during metal-based reduction, but return oxidation responses disappeared, indicative of a chemical reaction after exposure to CO2 without catalysis. Addition of H2O, a proton source, to the solutions under CO2 decreased the catalytic current of the group 6 carbonyls and had no effect on the responses of the group 7 carbonyls. The group 6 M(CO)6 species are notable in that that they are effective catalysts without the need for an added "non-innocent" ligand such as 2,2'-bipyridine.

Kinetic and structural studies, origins of selectivity, and interfacial charge transfer in the artificial photosynthesis of CO.

The effective design of an artificial photosynthetic system entails the optimization of several important interactions. Herein we report stopped-flow UV-visible (UV-vis) spectroscopy, X-ray crystallographic, density functional theory (DFT), and electrochemical kinetic studies of the Re(bipy-tBu)(CO)(3)(L) catalyst for the reduction of CO(2) to CO. A remarkable selectivity for CO(2) over H(+) was observed by stopped-flow UV-vis spectroscopy of [Re(bipy-tBu)(CO)(3)](-1). The reaction with CO(2) is about 25 times faster than the reaction with water or methanol at the same concentrations. X-ray crystallography and DFT studies of the doubly reduced anionic species suggest that the highest occupied molecular orbital (HOMO) has mixed metal-ligand character rather than being purely doubly occupied d(z)(2), which is believed to determine selectivity by favoring CO(2) (σ + π) over H(+) (σ only) binding. Electrocatalytic studies performed with the addition of Brönsted acids reveal a primary H/D kinetic isotope effect, indicating that transfer of protons to Re -CO(2) is involved in the rate limiting step. Lastly, the effects of electrode surface modification on interfacial electron transfer between a semiconductor and catalyst were investigated and found to affect the observed current densities for catalysis more than threefold, indicating that the properties of the electrode surface need to be addressed when developing a homogeneous artificial photosynthetic system.

Manganese catalysts with bulky bipyridine ligands for the electrocatalytic reduction of carbon dioxide: eliminating dimerization and altering catalysis.

With the goal of improving previously reported Mn bipyridine electrocatalysts in terms of increased activity and reduced overpotential, a bulky bipyridine ligand, 6,6'-dimesityl-2,2'-bipyridine (mesbpy), was utilized to eliminate dimerization in the catalytic cycle. Synthesis, electrocatalytic properties, X-ray diffraction (XRD) studies, and infrared spectroelectrochemistry (IR-SEC) of Mn(mesbpy)(CO)3Br and [Mn(mesbpy)(CO)3(MeCN)](OTf) are reported. Unlike previously reported Mn bipyridine catalysts, these Mn complexes exhibit a single, two-electron reduction wave under nitrogen, with no evidence of dimerization. The anionic complex, [Mn(mesbpy)(CO)3](-), is formed at 300 mV more positive potential than the corresponding state is formed in typical Mn bipyridine catalysts. IR-SEC experiments and chemical reductions with KC8 provide insights into the species leading up to the anionic state, specifically that both the singly reduced and doubly reduced Mn complexes form at the same potential. When formed, the anionic complex binds CO2 with H(+), but catalytic activity does not occur until a ~400 mV more negative potential is present. The Mn complexes show high activity and Faradaic efficiency for CO2 reduction to CO with the addition of weak Brønsted acids. IR-SEC experiments under CO2/H(+) indicate that reduction of a Mn(I)-CO2H catalytic intermediate may be the cause of this unusual "over-reduction" required to initiate catalysis.

Platinum(II) olefin hydroarylation catalysts: tuning selectivity for the anti-Markovnikov product.

Pt(II) complexes containing unsymmetrical (pyridyl)pyrrolide ligands are shown to catalyze the hydroarylation of unactivated alkenes with selectivity for the anti-Markovnikov product. Substitution on the pyrrolide portion of the ligand allows effective tuning of the selectivity to anti-Markovnikov alkylarene products, whereas substitution on the pyridyl portion can promote competitive alkenylarene production.

Oxygen-promoted C-H bond activation at palladium.

[Pd(P(Ar)(tBu)2)2] (1, Ar=naphthyl) reacts with molecular oxygen to form Pd(II) hydroxide dimers in which the naphthyl ring is cyclometalated and one equivalent of phosphine per palladium atom is released. This reaction involves the cleavage of both C-H and O-O bonds, two transformations central to catalytic aerobic oxidizations of hydrocarbons. Observations at low temperature suggest the initial formation of a superoxo complex, which then generates a peroxo complex prior to the C-H activation step. A transition state for energetically viable C-H activation across a Pd-peroxo bond was located computationally.

Elucidation of the selectivity of proton-dependent electrocatalytic CO2 reduction by fac-Re(bpy)(CO)3Cl.

A complete mechanism for the proton-dependent electrocatalytic reduction of CO2 to CO by fac-Re(bpy)(CO)3Cl that is consistent with experimental observations has been developed using first principles quantum chemistry. Calculated one-electron reduction potentials, nonaqueous pKa's, reaction free energies, and reaction barrier heights provide deep insight into the complex mechanism for CO2 reduction as well as the origin of selectivity for this catalyst. Protonation and then reduction of a metastable Re-CO2 intermediate anion precedes Brønsted-acid-catalyzed C-O cleavage and then rapid release of CO at negative applied potentials. Conceptually understanding the mechanism of this rapid catalytic process provides a useful blueprint for future work in artificial photosynthesis.

Manganese as a substitute for rhenium in CO2 reduction catalysts: the importance of acids.

Electrocatalytic properties, X-ray crystallographic studies, and infrared spectroelectrochemistry (IR-SEC) of Mn(bpy-tBu)(CO)3Br and [Mn(bpy-tBu)(CO)3(MeCN)](OTf) are reported. Addition of Brönsted acids to CO2-saturated solutions of these Mn complexes and subsequent reduction of the complexes lead to the stable and efficient production of CO from CO2. Unlike the analogous Re catalysts, these Mn catalysts require the addition of Brönsted acids for catalytic turnover. Current densities up to 30 mA/cm(2) were observed during bulk electrolysis using 5 mM Mn(bpy-tBu)(CO)3Br, 1 M 2,2,2-trifluoroethanol, and a glassy carbon working electrode. During bulk electrolysis at -2.2 V vs SCE, a TOF of 340 s(-1) was calculated for Mn(bpy-tBu)(CO)3Br with 1.4 M trifluoroethanol, corresponding to a Faradaic efficiency of 100 ± 15% for the formation of CO from CO2, with no observable production of H2. When compared to the analogous Re catalysts, the Mn catalysts operate at a lower overpotential and exhibit similar catalytic activities. X-ray crystallography of the reduced species, [Mn(bpy-tBu)(CO)3](-), shows a five-coordinate Mn center, similar to its rhenium analogue. Three distinct species were observed in the IR-SEC of Mn(bpy-tBu)(CO)3Br. These were of the parent Mn(bpy-tBu)(CO)3Br complex, the dimer [Mn(bpy-tBu)(CO)3]2, and the [Mn(bpy-tBu)(CO)3](-) anion.

A Redox Transmetalation Step in Nickel-Catalyzed C-C Coupling Reactions.

Ni-catalyzed C-H functionalization reactions are becoming efficient routes to access a variety of functionalized arenes, yet the mechanisms of these catalytic C-C coupling reactions are not well understood. Here, we report the catalytic and stoichiometric arylation reactions of a nickel(II) metallacycle. Treatment of this species with silver(I)-aryl complexes results in facile arylation, consistent with a redox transmetalation step. Additionally, treatment with electrophilic coupling partners generates C-C and C-S bonds. We anticipate that this redox transmetalation step may be relevant to other coupling reactions that employ silver salts as additives.

Anti-fibrotic activity of gold and platinum complexes - Au(I) compounds as a new class of anti-fibrotic agents.

Molecular gold(I) and platinum(II) species were examined for the inhibition of liver fibrosis and the hepatitis C virus (HCV). Determination of inhibition efficiency was conducted via morphological analysis, cell viability, western blot analysis, and quantitative reverse transcription polymerase chain reaction (RT-PCR). Auranofin and Ph3PAuCl demonstrated the greatest inhibition of liver fibrosis amongst the tested gold species in human hepatic stellate LX-2 cells. Western blot analysis indicated that auranofin and Ph3PAuCl prevent signal transducer and activator of transcription 3 (STAT3) phosphorylation, which may be a key connection to fibrosis and inflammation. Auranofin and Ph3PAuCl also reduced expression of HCV-nonstructural protein 3 (NS3) and HCV-NS5a proteins in a HCV subgenomic replicon system. These results demonstrate significant promise for the use of gold compounds in treating liver diseases such as HCV.

Calorimetric studies of the interactions of metalloenzyme active site mimetics with zinc-binding inhibitors.

The binding of drugs to metalloenzymes is an intricate process that involves several interactions, including binding of the drug to the enzyme active site metal, as well as multiple interactions between the drug and the enzyme residues. In order to determine the free energy contribution of Zn(2+) binding by known metalloenzyme inhibitors without the other interactions, valid active site zinc structural mimetics must be formed and binding studies need to be performed in biologically relevant conditions. The potential of each of five ligands to form a structural mimetic with Zn(2+) was investigated in buffer using Isothermal Titration Calorimetry (ITC). All five ligands formed strong 1 : 1 (ligand : Zn(2+)) binary complexes. The complexes were used in further ITC experiments to study their interaction with 8-hydroxyquinoline (8-HQ) and/or acetohydroxamic acid (AHA), two bidentate anionic zinc-chelating enzyme inhibitors. It was found that tetradentate ligands were not suitable for creating zinc structural mimetics for inhibitor binding in solution due to insufficient coordination sites remaining on Zn(2+). A stable binary complex, [Zn(BPA)](2+), which was formed by a tridentate ligand, bis(2-pyridylmethyl)amine (BPA), was found to bind one AHA in buffer or a methanol : buffer mixture (60 : 40 by volume) at pH 7.25 or one 8-HQ in the methanol : buffer mixture at pH 6.80, making it an effective structural mimetic for the active site of zinc metalloenzymes. These results are consistent with the observation that metalloenzyme active site zinc ions have three residues coordinated to them, leaving one or two sites open for inhibitors to bind. Our findings indicate that Zn(BPA)X2 can be used as an active site structural mimetic for zinc metalloenzymes for estimating the free energy contribution of zinc binding to the overall inhibitor active site interactions. Such use will help aid in the rational design of inhibitors to a variety of zinc metalloenzymes.

Hemilability of P(X)N-type ligands (X = O, N-H): rollover cyclometalation and benzene C-H activation from (P(X)N)PtMe2 complexes.

The thermolyses of ((tBu)P(O)N)PtMe2 (, (tBu)P(O)N = (di-tert-butylphosphinito)pyridine) and ((tBu)P(N-H)N)PtMe2 (, (tBu)P(N-H)N = (di-tert-butylphosphino)-2-aminopyridine) in benzene-d6 were investigated. With ((tBu)P(O)N)PtMe2, the product of a rollover cyclometalation of the pyridyl ring was observed in 80% yield along with formation of CH4. In contrast, thermolysis of ((tBu)P(N-H)N)PtMe2 resulted in competing rollover cyclometalation and intermolecular benzene C-H activation with production of a mixture of CH4 and CH3D.

Carbon monoxide release catalysed by electron transfer: electrochemical and spectroscopic investigations of [Re(bpy-R)(CO)4](OTf) complexes relevant to CO2 reduction.

[Re(bpy-tBu)(CO)4](OTf) (bpy-tBu = 4,4'-di-tert-butyl-2,2'-bipyridine, OTf = trifluoromethanesulfonate) (1) and [Re(bpy)(CO)4](OTf) (bpy = 2,2'-bipyridine) (2) were synthesized and studied as proposed intermediates in the electrocatalytic reduction of carbon dioxide (CO2) by Re(bpy-R)(CO)3X. Both compounds demonstrated increased current responses in cyclic voltammograms under CO2. Complex 1 was also characterized by X-ray crystallography. Infrared-spectroelectrochemistry (IR-SEC) of 1 and 2 indicated that upon exposure of the cationic tetracarbonyl compounds to a reducing potential, a CO ligand is labilised and [Re(bpy-R)(CO)3(CH3CN)](+) species are formed. This is proposed to occur via an electron-transfer-catalysed process wherein a catalytic amount of reduced species propagates a ligand exchange reaction. Addition of a catalytic amount of potassium intercalated graphite (KC8), a chemical reductant, to a solution of 1 or 2 also yielded quantitative formation of [Re(bpy-R)(CO)3(CH3CN)](+), which indicates that the CO loss is catalysed by electron transfer, and not the electrode itself.